Metabolic tumor volume and sites of organ involvement predict outcome in NSCLC immune-checkpoint inhibitor therapy.

PURPOSE: The purpose of this study was to assess the ability of pretreatment PET parameters and peripheral blood biomarkers to predict progression-free survival (PFS) and overall survival (OS) in NSCLC patients treated with ICIT. METHODS: We prospectively included 87 patients in this study who underwent pre-treatment [18F]-FDG PET/CT. Organ-specific and total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured using a semiautomatic software. Sites of organ involvement (SOI) were assessed by PET/CT. The log-rank test and Cox-regression analysis were used to assess associations between clinical, laboratory, and imaging parameters with PFS and OS. Time dependent ROC were calculated and model performance was evaluated in terms of its clinical utility. RESULTS: MTV increased with the number of SOI and was correlated with neutrophil and lymphocyte cell count (Spearman's rho = 0.27 or 0.32; p =.02 or 0.003; respectively). Even after adjustment for known risk factors, such as PD-1 expression and neutrophil cell count, the MTV and the number of SOI were independent risk factors for progression (per 100 cm3; adjusted hazard ratio [aHR]: 1.13; 95% confidence interval [95%CI]: 1.01-1.28; p =.04; single SOI vs. ≥ 4 SOI: aHR: 2.26, 95%CI: 1.04-4.94; p =.04). MTV and the number of SOI were independent risk factors for overall survival (per 100 cm3 aHR: 1.11, 95%CI: 1.01-1.23; p =.03; single SOI vs. ≥ 4 SOI: aHR: 4.54, 95%CI: 1.64-12.58; p =.04). The combination of MTV and the number of SOI improved the risk stratification for PFS and OS (log-rank test p <.001; C-index: 0.64 and 0.67). CONCLUSION: The MTV and the number of SOI are simple imaging markers that provide complementary information to facilitate risk stratification in NSCLC patients scheduled for ICIT.

Bronchoscopic diagnosis and treatment of endobronchial carcinoid: case report and review of the literature.

Carcinoid tumours are rare neuroendocrine neoplasms that mostly occur in younger adults with low tendencies to metastasise. Based on their histological characteristics, they are divided into typical and atypical subtypes. The most common presenting symptoms are due to central airway obstruction. The first step in the diagnostic assessment should be a computed tomography (CT) scan, as it provides information both for local tumour extent and lymph node involvement. Bronchoscopy is the main tool for histological confirmation, evaluation of bronchial wall invasion and removal of endobronchial manifestation with subsequent resolution of atelectasis. Endobronchial ultrasound may be necessary to rule out lymph node metastasis. Somatostatin receptor scintigraphy in combination with CT can rule out further metastatic disease.Surgical resection using parenchyma-sparing techniques remains the gold standard for treatment. For selected patients, endobronchial therapy could be an alternative for minimal invasiveness. Long-term follow-up is suggested due to the high likelihood of recurrence.Here, we describe our clinical experience in a 35-year-old male patient who originally presented with haemoptysis and a central polypoid tumour in the left main bronchus revealed by a CT scan. The histological characteristics were indicative of a typical carcinoid. The patient was treated using an endobronchial approach only. No complications and no recurrences have been observed in a follow-up of 2 years.

Prevalence and Associations of Illicit Drug and Polydrug Use in People Living with HIV in Vienna.

We aimed to determine the prevalence of drug and polydrug use in people living with HIV in Austria for the first time for which a two center cross-sectional study was performed. Participants were recruited from consecutive patients during their regularly scheduled visits. In total 438 participants were included in the analysis. For this study we used paper-pencil and online-based questionnaires. The prevalence of illicit drug use was 60.5%; with cannabis use at 31.5%, nitrates at 31.5%, sildenafil/tadalafil at 24% and cocaine at 14%, being the most used substances. Use of more than one substance (polydrug) in drug users was 69.4% or 42.0% in the total study population. Younger age, male gender, and living in an urban area were associated with drug use. Moreover, drug use during clubbing and sex, HIV therapy non-adherence and younger age were associated with polydrug use. Drug users reported condomless sex in 42.4% and performing sexual acts they would not do sober in 44.1%. Results indicate a high prevalence of illicit drug use in PLWHIV in Austria. New research focusing on illicit drug use in PLWHIV should focus on the use of substances during sex and surrounding practices.

Genetic profiling of putative breast cancer stem cells from malignant pleural effusions.

A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were further sorted for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally, sphere forming efficiency of CSC and non-CSC subpopulations was determined. In order to genetically characterize the different tumor subpopulations, DNA was isolated from pleural effusions before and after cell sorting, and compared with corresponding DNA copy number profiles from primary tumors or bone metastasis using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells had a higher potential to form spheres when compared to CSC subpopulations. In most cases, cell sorting did not yield sufficient cells for copy number analysis. A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant copy number profiles similar to the respective primary tumor. However, most sorted subpopulations showed a balanced profile indicating an insufficient amount of tumor cells and low sensitivity of the sequencing method. Finally, we were able to establish a long term cell culture from one pleural effusion sample, which was characterized in detail. In conclusion, we confirm that pleural effusions are a suitable source for enrichment of putative CSC. However, sequencing based molecular characterization is impeded due to insufficient sensitivity along with a high number of normal contaminating cells, which are masking genetic alterations of rare cancer (stem) cells.

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients.

INTRODUCTION: The incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients. METHODS: A total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: Two patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%. CONCLUSION: LFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available. TRIAL REGISTRATION: ClinicalTrials.gov NCT02058316. Registered 20 January 2014.

Progressive alveolar echinococcosis after discontinuation of anthelmintic therapy.

We report a case of a female patient with alveolar echinococcosis (AE) who presented with progressive pulmonary and hepatic lesions and had a fatal outcome. AE affecting the liver, the lungs and the brain had been diagnosed 20 years ago and treated successfully with albendazole and stereotactic gamma knife therapy. Due to severe hair loss albendazole was stopped 14 years before presentation. Lesions had remained stable in imaging studies for at least 11 years, but then had started to progress. Lifelong anthelmintic maintenance therapy and regular follow-up may therefore be crucial in order to prevent such a dramatic clinical course.

Novel technique for in situ cold perfusion in laparoscopic partial nephrectomy.

BACKGROUND: Following clamping of the renal hilus, warm ischemia is an issue in laparoscopic partial nephrectomy. If ischemia longer than 30 min is anticipated, special protective measures are needed. The aim of this study was to develop a solely laparoscopic technique for in situ cold perfusion of kidneys during laparoscopic partial nephrectomy to increase the tolerance of renal parenchyma to ischemic damage in a porcine model. METHODS: Six animals were used in this study. We tried to develop a technique that allowed us to cannulate the renal artery, introduce a catheter to perform an in situ cold perfusion and-the most important feature-secure the catheter throughout the laparoscopic partial nephrectomy. RESULTS: A modified laparoscopic vascular bulldog clamp was ultimately ideal to fulfil expectations. In five pigs, a successful partial nephrectomy in in situ perfusion was performed. The median warm ischemia time, starting from occlusion of the renal artery and vein to the commencement of cold perfusion, was 130 s (range 75-165 s). The subsequent median cold ischemia time in which a partial nephrectomy was simulated was 42 min (range 26-52 min). CONCLUSIONS: The newly developed technique expands the armamentarium of the urologist in laparoscopic partial nephrectomy, if the anticipated time of ischemia exceeds 30 min and renal hypothermia is indicated.

Optimized haemostasis in nephron-sparing surgery using small-intestine submucosa.

BACKGROUND: The indications for nephron-sparing surgery are expanding constantly. One major contributing fact for this development is the improvement of haemostatic techniques following excision of the tumor. Nevertheless, postoperative bleeding complications still occur. To prevent this, we prospectively studied the effect of application of small-intestine submucosa (SIS) over the renal defect. METHODS: We performed 55 nephron-sparing surgeries applying SIS between 08/03 and 10/06 in 53 pts. (mean age: 59 yrs., range 29 - 79 yrs.). After resection of the renal tumor and application of a haemostyptic agent, we used SIS to secure and apply compression on the defect. RESULTS: The final pathology revealed clear-cell and papillary carcinoma, papillary adenoma, oncocytoma, and angiomyolipoma in 39 (70.9%), 6 (10.9), 1 (1.8%), 2 (3.6%) and 7 (12.7%) patients, respectively. The 45 malignant lesions (81.8%) were classified as pT1a and pT1b in 35 (77.8%) and 10 (22.2%) patients, respectively. The median tumor size was 4.5 cm (range: 1.3 - 13 cm). The median operating time was 186 min (range: 90 - 260 min). 18 (32.7%) procedures were performed without ischemia. 23 (41.8%) and 14 (25.5%) cases were operated in in-situ cold and warm ischemia, respectively. The median intraoperative blood loss was 730 cc (range: 100 - 2500 cc). No open operative revision was indicated due to postoperative bleeding complications. Furthermore, there was no necessity to substitute persistent blood loss from the drains postoperatively. No urinoma occurred. CONCLUSION: SIS is a highly effective and easy-to-use instrument for preventing postoperative bleeding and urinary fistula complications in nephron-sparing surgery.